Table 2.
Representative primary studies and the inferences they support.
| Study | Signal/destination | Model and timing | Source/route approach | Permitted source/route inference and causal-role evidence |
|---|---|---|---|---|
| Stanley et al. (20) | Viable bacteria; lung and peripheral tissues | Mouse ischemic stroke; permeability preceded dissemination; exact interval NR | 16S source analysis, paired tissues, oral inoculation | Source/route inference: links a small-intestinal source to a post-stroke lung community in this model; it does not establish a universal human route, lymph-versus-blood movement, or direct brain delivery. Causal-role evidence: gut-to-periphery dissemination is demonstrated, but a role in secondary brain injury was not tested. |
| Oyama et al. (23) | Viable bacteria; extra-intestinal organs | Transient MCAO; first 72 h after stroke | Functional permeability, culture/fluorescence in situ hybridization (FISH), mucosal immune assessment | Source/route: junctional change without consistent functional leak/translocation. Causal role: not demonstrated in this model. |
| Kurita et al. (57) | LPS; plasma and ischemic brain | Diabetic db/db mice after transient MCAO; intestinal permeability assessed before and 3 h after MCAO; brain endpoints mainly at 24 h | Barrier assessment, plasma LPS, brain signaling, non-absorbable antibiotic intervention | Source/route: gut-associated endotoxemia in diabetic mice; brain route unresolved. Causal role: polymyxin supports a contribution in this model, not a traced gut-to-brain effect. |
| Peh et al. (24) | Bacterial-like structures; blood and ischemic brain | Photothrombotic stroke/MCAO; bacterial signals measured at 24 and 72 h, with key quantification at 24 h; germ-free comparison | Immunostaining, absolute PCR, germ-free comparison, sympathetic inhibition | Source/route: microbiota-dependent brain-associated signals; gut-to-brain origin and viability unresolved. Causal role: necessity for injury not established. |
| Diaz-Marugan et al. (95) | Opportunistic commensals; post-stroke lung | Controlled post-stroke lung-infection model; exact sampling interval NR | Infection and gut-community analyses | Source/route: gut Enterobacteriaceae expansion was not required for lung colonization under the tested conditions. Causal role: the findings did not support a requirement for the gut bloom for this endpoint. |
| Benakis et al. (70) | Community-dependent immune programming; intestine/meninges | Experimental stroke mice; acute immune-cell endpoints; exact interval NR | Microbiota and gamma-delta T-cell manipulation | Source/route: microbiota-dependent peripheral immune relay; no direct brain entry. Causal role: supported by microbiota/T-cell perturbation in mice. |
| Huang et al. (58) | Intestinal epithelial TLR4 relay; gut and brain injury | Acute MCAO with recovery cohorts; exact sampling intervals NR | Intestinal epithelial vs brain-specific deletion, pharmacology, rescue | Source/route: epithelial TLR4 relay; ligand and transport route unresolved. Causal role: deletion/pharmacology/rescue support compartment involvement. |
| Yuan et al. (54) | Acetate-related phenotype; plasma/cortex/recovery | Older adults with stroke plus aged-mouse transfer model; human sampling window NR; mouse recovery/angiogenesis followed longitudinally | Human association plus donor-microbiota transfer and angiogenesis/lymphatic measurements | Source/route: aged-mouse transfer and human acetate association; patient source unresolved. Causal role: community-transfer effect supported; acetate necessity not established. |
| Yao et al. (39) | Oral and gut communities/metabolites | Human oral-plaque/stool cohort; acute sampling window NR | Full-length 16S sequencing and metabolomics across niches | Source/route: oral/stool overlap; no organismal transfer or systemic source shown. Causal role: association only. |
| He et al. (38) | Oropharyngeal and gut communities; systemic inflammation | acute ischemic stroke (AIS) with or without preceding infection; collection window NR | Oropharyngeal and gut sequencing plus inflammatory markers | Source/route: oral and gut dysbiosis associate with outcome; systemic source unassigned. Causal role: observational association. |
| Li et al. (55) | Gut community/coagulation phenotype; outcome | Human AIS prediction cohort; acute study window; exact collection interval NR | Microbiota plus coagulation-based prediction model | Source/route: predictive model, without tissue or route tracing. Causal role: not established. |
| Chen et al. (101) | Indole-3-propionic acid/TREM2-NLRP3 pathway | Experimental post-stroke model; intervention and pathway endpoints; exact interval NR | Defined microbial/metabolite intervention and pathway analysis | Source/route: defined intervention supports a metabolite pathway in one model; human source/route unresolved. Causal role: experimental contribution, not a universal gut-to-brain mechanism. |
Studies are organized according to the primary question they address. The final column distinguishes source/route inference from causal-role evidence and indicates whether causal testing was performed. NR indicates that a precise sampling interval was not reported or separately specified; relative timing is retained where reported in the original study.